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Biophysical cellular cues as predictive biomarkers of bladder cancer

dc.contributor.advisorCalejo, Isabel
dc.contributor.advisorCanadas, Raphael
dc.contributor.advisorFerraz, Ricardo
dc.contributor.authorAzevedo, Ana Catarina Correia
dc.date.accessioned2026-02-25T12:09:15Z
dc.date.available2026-02-25T12:09:15Z
dc.date.issued2025-07-24
dc.description.abstractBladder cancer (BC) is a common neoplasm characterized by high recurrence and rapid progression. Current diagnostic methods have limitations: cytoscopy is invasive and expensive, and urinary cytology is not very sensitive for low-grade tumors. Therefor, there is increasing interest in non-invasive biophysical biomarkers. In this dissertation, label-free methodologies were used, such as imaging flow cytometry (IFC), eletrophoretic light scattering (ELS) and acoustofluidics, which were essential for the deepening of the morphological and biophysical characteristics of BC cells, which were relevant for their label-fre separation from other cells commonly found in urine. IFC allowed the quantification of several morphological parameters in five urinary populations, such as cancerous epithelial cells, non-cancerous epithelial cells, squamous cells, erythrocytes, and lymphocytes. The data obtained with this technique also allowed us to infer critical biophysical properties for acoustic migration, particularly cell density. The increased diameter and reduced contrast and gradient RMS of cancer epitelial cells indictaed less internal organization and compaction, indicating lower density than, erythrocytes, and lymphocytes, that promotes different accoustic mobility between cell types. ELS outlined distinct zeta potential profiles, revealing that there could be a correlation between epithelial-mesenchymal transition (EMT) and tumor cell load, with a tendency to be more, negative values in cells with a more mesenchymal profile. EMT unscored cell lines presented intermediate values. Clinical isolates from bladder tumours exhibited variation consistente with that was observed in cell lines, suggesting zeta potential as a functional biomarker of tumor progression. Finally, aoustofluidics allowed the separation of epitelial cancer cells from the other cell populations presente in clinical urine samples. The results of this technique were compared with histological (reference control) and cytological (technique for direct comparison) results. Cytology obtaines high specificity, but limited sensivity; while acoustofluidics received superior sensivity, although with lower specificity. However, considering that almost 90% of the studied clinical cases were histologically positive, the high sensivity of the acoustic seperation technique is clinically more relevant.eng
dc.description.sponsorship"CELLETED" (C124-10322)
dc.identifier.tid204179980
dc.identifier.urihttp://hdl.handle.net/10400.22/31907
dc.language.isoeng
dc.relation"CELLO" (2022.05237.PTDC)
dc.rights.uriN/A
dc.subjectBladder cancer
dc.subjectBiomarkers
dc.subjectBiophysiscs
dc.subjectAcoustofluidics
dc.titleBiophysical cellular cues as predictive biomarkers of bladder cancereng
dc.typemaster thesis
dspace.entity.typePublication
thesis.degree.nameMestre em Bioquímica em Saúde-Bioquímica Aplicada

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